1. Field Of The Invention
This invention relates generally to apparatus for measuring the concentrations of electrolyte components such as sodium, potassium, and others in fluid samples, such as biological fluids. More particularly, the invention relates to apparatus for electrically measuring the concentrations of selected electrolytes in such samples and for generating optical signals representative of the measured concentrations of the selected electrolytes. Apparatus embodying the present invention is particularly advantageous for use in conjunction with existing automated assay instruments which employ optical sources and detectors to read assays and optically encoded data.
2. Description Of Related Art
It is often necessary or desirable in determining and evaluating the condition of a patient to determine the concentration of certain electrolytes in the patient's system. Typically, the presence and concentration of electrolytes is determined by analyzing a sample of whole blood or blood serum taken from the patient. Common electrolyte components of interest include potassium, sodium, chloride, carbon dioxide, lithium, ammonium, and pH, to name a few.
Traditionally, such electrolytes have been detected and measured using flame spectrophotometric techniques. Generally, in flame spectrophotometry, a chemical composition is prepared from a sample containing the electrolyte or electrolytes of interest. The composition is then combusted and optical measurements of the resulting flame are made. The spectral characteristics of the flame are then analyzed to determine the presence and concentration of the electrolytes of interest in the sample The value of flame spectrophotometric techniques is limited by their ability to operate on serum only and not whole blood. In addition, in flame spectrophotometry, it is critical but very difficult to precisely control the combustion of the prepared compound. Consequently, with this technique it is typically not possible to obtain a high degree of accuracy and repeatability, both of which are highly desirable characteristics.
In order to overcome the drawbacks and limitations associated with traditional flame spectrophotometric techniques, ion selective electrode apparatus and measuring techniques have been developed. An ion selective electrode typically includes a specially formulated chemical membrane connected to one of a pair of electrodes. The other electrode typically serves as a reference. The membrane is specially formulated to have an affinity for a selected electrolyte of interest. When the membrane is exposed to a fluid sample containing the selected electrolyte of interest, it attracts the electrolyte and builds up an ionic charge which results in a measurable voltage differential between the two electrodes. The electrodes may be connected to electrical circuitry which converts the voltage differential into an electrical signal representative of the concentration of the selected electrolyte. Ion selective electrodes having an affinity for most if not all of the commonly known electrolytes have been developed. Ion selective electrodes have the ability to measure electrolyte concentrations directly from whole blood samples without the requirement of first filtering the blood sample to obtain serum. In addition, ion selective electrode technology provides highly sensitive, accurate, and repeatable electrolyte measurements.
Similarly to ion selective electrodes, chemical field effect transistors (Chem FET's) have also been developed and have been successfully employed in measuring electrolytes in fluid biological samples. Like ion selective electrodes, Chem FET's employ specially formulated chemical membranes having affinities for particular electrolytes of interest. However, unlike ion selective electrodes, which are completely passive devices, Chem FET's include a field effect transistor (FET) which is controlled by the ion charge on a membrane to allow current flow between the source and drain of the FET. This current flow is measurable and can be related to the concentration of the electrolyte of interest in the sample. Alternatively, Chem FET's have been utilized in a voltage mode by feeding back the drain-source current to vary the gate voltage and maintain the drain-source current constant. In this mode, the gate voltage varies measurably with electrolyte concentration Like ion selective electrodes, Chem FET's typically provide more accurate electrolyte measurements than traditional flame spectrophotometric techniques.
It is advantageous to include ion selective electrode or similar Chem FET technology in existing automated assay instruments in order to extend the range of assays which such instruments can perform to include electrolytes. However, such instruments have typically been designed to measure assays optically and are therefore fundamentally incompatible with ion selective electrode and related Chem FET technology which is based upon electrical measurement of assays. Thus, in the past in order to incorporate the two technologies, it has typically been necessary to extensively modify existing instruments by the addition of special electronics in order to take advantage of ion selective electrode or Chem FET technology. Attendant with the requirement of such modifications have been increased cost, inconvenience, and sometimes unreliability.
The present invention seeks to overcome the foregoing drawbacks and limitations of the prior art by providing apparatus for measuring electrolyte concentrations in biological samples which takes advantage of preferred ion selective electrode technology and techniques and which at the same time is compatible with existing automated assay instruments of the type utilizing conventional optical reader technology. It is a significant feature of the invention that the apparatus requires little if any modification of existing automated assay instruments on which it is to be used. Advantageously, the apparatus provides the flexibility, sensitivity, accuracy, and repeatability associated with ion selective electrode technology. At the same time, the apparatus reduces costs by providing the ability to utilize the optical assay reading or optical code reading apparatus present in existing automated assay instruments without modification. Another significant feature of the invention is the relatively low cost at which the apparatus can be manufactured and used. Still other advantages and features of the invention will become apparent from the detailed description of the presently preferred embodiments thereof which is set forth below.